Schizophrenia is a devastating form of psychopathology, with a lifetime prevalence worldwide of 0.5%-1%. Twin and adoption studies suggest that both genetic and environmental factors influence susceptibility (see, e.g., Tsuang, M. T. et al., Schizophr. Res. 4(2):157-71 (1991); Tienari, P. J. and Wynne, L. C., Ann. Med. 26(4):233-7 (1994); Franzek, E. and Beckmann, H., Am. J. Psychiatry 155(1):76-83 (1998); Tsuang, M. T., J. Biomed. Sci. 5(1):28-30 (1998)). Among first-degree relatives, the risk has been reported to vary from 6% in parents, to 10% in siblings, and to 13% in children of schizophrenic individuals; if one of the parents is also schizophrenic, the risk to siblings increases to 17%, and children of two schizophrenics have a risk of 46% of developing the illness (McGue, M. and Gottesmann, I. I., Eur. Arch. Psychiatry Clin. Neurosci 240:174-181 (1991); see also, e.g., Lim, L. C. and Sim, L. P., Singapore Med. J. 33(6):645-7 (1992)). The mode of transmission, however, remains uncertain.
Reports of suggestive linkage to several loci have been published, including loci on chromosomes 3, 5, 6, 8, 10, 13, 20, 22 and the X chromosome (see, e.g., for chromosomes 3p and 8p, Pulver, A. E., et al., Am. J. Med. Genet. 60(4):252-60 (1995); for chromosomes 5q, 6p and 8p, Kendler, K. S. et al., Am. J. Med. Genet. 88(1):29-33 (1999); for chromosomes 5q, 6p, 8p, 20p and 22q, Hovatta, I. et al., Mol. Psychiatry. 3(5):452-7 (1998); for chromosome 6p, Schwab, S. G. et al., Nat. Genet. 11(3):325-7 (1995), Brzustowicz, L. M. et al., Am. J. Hum. Genet. 61(6):1388-96 (1997) and Cao, Q. et al., Genomics 43(1):1-8 (1997); for chromosomes 6 and 8, Straub, R. E. et al., Cold Spring Harbor Symp. Quant. Biol 61I:823-33 (1996); for chromosome 8, Kendler, K S. et al., Am. J. Psychiatry 153(12):1534-40 (1996); for chromosome 10, Straub, R. E. et al., Am. J. Med. Genet. 81(4):296-301 (1998) and Schwab, S. G. et al., Am. J. Med. Genet. 81(4):302-307 (1998); for chromosome 13, Lin, M. W. et al., Psyciatr. Genet. 5(3):117-26 (1995); Lin, M. W. et al., Hum. Genet. 99(3):417-420 (1997) and Blouin, J. L. et al., Nat. Genet. 20(1):70-73 (1993) (8 and 13); for chromosome 22, Gill, M. et al., Am. J. Med. Genet. 67(1):40-45 (1996) and Bassett, A. S. et al., Am. J. Med. Genet. 81(4):328-37 (1998); and for the X chromosome, Milunsky, J. et al., Clin. Genet. 55(6):455-60 (1999)).